Search for chlorinated sesquiterpene lactones in the neurotoxic thistle Centaurea solstitialis by liquid chromatography-mass spectrometry, and model studies on their possible artifactual formation

An HPLC method has been developed for the analysis of sesquiterpene lactones of the neurotoxic plant Centaurea solstitialis (Asteraceae). The presence of sesquiterpene lactone chlorohydrins in extracts was investigated by means of liquid chromatography-thermospray mass spectrometry. In contrast to earlier reports of a series of mono- and dichlorohydrins from this plant, traces only of two monochlorohydrins could be detected in lipophilic extracts. Model studies carried out with extracts and with the genuine sesquiterpene diepoxide repin and its epimer subluteolide showed that (i) monochlorohydrins can be formed in CHCl3 under usual laboratory conditions; (ii) the epoxide moiety at C-4 of the sesquiterpenes is extremely labile, reacting immediately and quantitatively with traces of HCl to the corresponding monohydrins; (iii) epoxide ring opening at the acyl side chain occurs only at higher HCl concentrations. Confirmation of the peak identity was obtained by the isotope ratio of chlorinated compounds and comparison with authentic samples. The structures of the mono- and dichlorohydrins were established by NMR spectroscopy.     

Basic fibroblast growth factor promotes the proliferation of human megakaryocyte progenitor cells

Basic fibroblast growth factor (bFGF), a multifunctional growth factor produced by bone marrow stromal cells, is known to be a potent modulator of hematopoiesis. Because bFGF is present in both human megakaryocytes (MKs) and platelets, we have hypothesized that this growth factor might affect human megakaryocytopoiesis. To test this hypothesis, either low density bone marrow (BM) cells (LDBM), a human BM subpopulation (CD34+ DR+) enriched for the colony-forming unit megakaryocyte (CFU-MK) or a BM subpopulation (CD34+ DR-) enriched for the more primitive burst-forming unit megakaryocyte (BFU-MK) were assayed in the presence of this growth factor. The effect of bFGF on MK colony formation differed according to the cell population assayed. bFGF alone had on MK colony-stimulating activity (MK-CSA) when either CD34+ DR+ or CD34+ DR- BM cells were cloned, but exhibited MK-CSA equivalent to that of interleukin-3 (IL-3) when LDBM cells were used as the target cell population. The MK-CSA of bFGF was inhibited by the addition of neutralizing antisera to either IL-3 and/or granulocyte-macrophage colony-stimulating factor (GM-CSF) but not IL-6. The addition of excess amounts of either IL-3 or GM-CSF to cultures containing bFGF plus anti-IL-3 or anti-GM-CSF reversed the inhibition by the corresponding antisera. The addition of bFGF and IL-3 to assays containing CD34+ DR+ or CD34+ DR- cells increased the size of both CFU-MK- and BFU-MK-derived colonies, respectively, when compared with assays containing IL-3 alone. This increase in MK colony size mediated by bFGF was not affected by addition of either an anti-GM-CSF or anti-IL-6 neutralizing antisera. When LDBM cells were assayed, bFGF alone increased CFU-MK-derived colony size when compared with control values. However, this potentiation of MK colony size by bFGF could be reversed by the addition of either anti-IL-3 or anti-GM-CSF but not anti-IL-6 antisera. In addition, the effects of bFGF and IL-3 on the size of MK colonies cloned from LDBM were not additive. These results suggest that bFGF affects human megakaryocytopoiesis by directly promoting MK progenitor cell proliferation and stimulating BM accessory cells to release growth factor(s) with MK-CSA, such as IL-3 and GM-CSF. We conclude that bFGF, likely produced by cellular components of the BM microenvironment, plays an important role in the control of human megakaryocytopoiesis.     

Efficacy and safety of nifedipine versus magnesium sulfate in the management of preterm labor: a randomized study

OBJECTIVE: Our purpose was to establish the efficacy and safety of nifedipine versus magnesium sulfate in arresting preterm labor and the efficacy of nifedipine versus terbutaline in preventing recurrent labor. STUDY DESIGN: Singleton pregnancies at < 34 weeks in preterm labor were randomized to either oral nifedipine or intravenous magnesium sulfate. In case of tocolysis failure ritodrine was added. After labor was arrested, the patients in the nifedipine group were maintained on oral nifedipine, and those in the magnesium sulfate group were treated with oral terbutaline until completing 34 weeks. RESULTS: Of 100 patients 80 were considered eligible, of whom 39 were randomized to the nifedipine group. Both groups were comparable in terms of a number of entry variables, including cervical examination, contraction frequency, and gestational age. Both drugs were equally effective in arresting labor and delaying delivery > 48 hours, 92% versus 93%. Both study groups had a similar incidence of side effects, although four (10%) of magnesium sulfate-treated patients required drug discontinuation because of severe symptoms. Nifedipine was as effective as terbutaline in preventing recurrent labor, 26% versus 24%, and in achieving a gestation > 34 weeks, 62% versus 68%. CONCLUSIONS: Oral nifedipine is as effective as magnesium sulfate and terbutaline in arresting and preventing idiopathic preterm labor.     

Upper airway changes in snorers and mild sleep apnea sufferers after uvulopalatopharyngoplasty (UPPP)

OBJECTIVES: We used upper airway (UA) imaging in 20 patients to determine (1) whether an effective enlargement of the UA is obtained after uvulopalatopharyngoplasty (UPPP), and (2) whether UA modifications explain the results of such surgery. METHODS: Cephalometric measurements were made to assess the posterior airway space, the length and width of the soft palate, and the distance between the hyoid bone and the mandibular plane. Pharyngeal CT measured the airway cross-sectional area (CSA) at each 10-mm slice from 10 mm above (-10) to 40 mm below (+40) the hard palate. Polysomnography was performed before and after surgery (10+/-10 [SD] months). Good responders were defined by an apnea-hypopnea index (AHI) of <10 postsurgery or, in patients in whom AHI was initially <10, a reduction of AHI >50% of the initial AHI. RESULTS: Twenty patients (age=45+/-11 years) were studied. For the whole group, the mean body mass index (26+/-4 kg/m2) and AHI (14+/-13 vs 18+/-16/h) were unchanged after UPPP. The results of the surgery were mediocre with 7 good responders (35%) and 13 nonresponders (65%) defined by polysomnographic criteria. The only changes on UA imaging for the group as a whole after UPPP were decrease in length (40+/-6 vs 29+/-5 mm, p< or =0.0006) and increase in width of the soft palate (11.5+/-2.7 vs 13.6+/-3.5 mm, p< or =0.006). The increase or decrease in minimal CSA at the oropharyngeal (OP) level after UPPP was significantly correlated with the change in AHI (r=-0.54, p<0.02). Moreover, the changes in CSA obtained at the OP level were significant only in the patients who responded favorably to UPPP (7 vs 13 nonresponders). CONCLUSIONS: Postoperative OP enlargement is associated with a good outcome of UPPP. Persistent narrowing in nonresponders could be due to the increase in soft palate width after surgery.     

Cyclosporine A decreases kallikrein and BK2 mRNA expression in the rat renal cortex

The effect of subcutaneous injection of cyclosporine (20 mg/kg/day for 3 days) on the expression of kallikrein (Kal) and bradykinin 2 receptor (BK2) mRNA in the rat renal cortex was examined. CsA decreased significantly Kal and BK2 mRNA expression in the kidney cortex. These results indicate that the kallikrein-kinin system may participate in the genesis or the aggravation of the renal haemodynamic effect induced by long term administration of CsA.